Medical and socio-economic aspects of long term therapy of open angle glaucoma.

Hundred patients of open angle glaucoma (OAG) who were on any one of the three drugs pilocarpine, timolol and epinephrine--for an average period of 3.3 years were chosen. Proforma regarding socio-economic status and the patients' reaction to long-term medication were recorded. Though the objective and subjective effects of long term medication were negligible the financial constraints were considerable. More than 70% patient would prefer laser's and surgery because of the cumbersome schedule and financial burden. The visit to the clinic was a time consuming process suggesting a lack of adequate glaucoma follow-up at the peripheral level. The study reflects a need for reorientation of glaucoma management.     

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

Purpose:To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods:Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results:The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0.0147) and NTG (4/28, 14.2%, p = 0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p = 0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p = 0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p = 0.0076), and a significantly higher rate of surgery and/or laser history (p = 0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. Conclusions:Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open-angle glaucoma in this Japanese population.     

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

PURPOSE: To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. RESULTS: The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p=0.0147) and NTG (4/28, 14.2%, p=0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p=0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p=0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p=0.0076), and a significantly higher rate of surgery and/or laser history (p=0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. CONCLUSIONS: Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open- angle glaucoma in this Japanese population.     

The vascular pattern of the optic nerve and its potential relevance in glaucoma

Evidence that vascular factors contribute to the pathogenesis and development of glaucomatous optic neuropathy continues to accumulate. A higher than expected prevalence of systemic vascular disorders in individuals with glaucoma has been documented. New sophisticated in vivo analysis techniques, such as ultrasound color Doppler imaging, suggest that decreased blood flow velocity and increased vascular resistance are present in the vessels serving the optic nerve of human subjects with glaucoma, implying the presence of either organic or functional vascular disorders in these individuals. Recognizing that different analysis techniques have led to conflicting observations, experimental models have been developed to provide an additional tool with which to interpret the effects of compromised optic nerve perfusion.     

Resting energy expenditure in vasospastic subjects and its potential relevance in glaucoma

BACKGROUND: Peripheral vasospastic syndrome is frequently encountered in normal tension glaucoma patients. We tested the hypothesis as to whether peripheral vascular spastic tendency is due to an attempt to preserve body heat in subjects with reduced resting energy expenditure. PATIENTS AND METHODS: Twenty healthy non-smoking female individuals were enrolled into the study. Subjects were classified as having vasospasm (10 subjects) if they related a clear history of frequent cold hands, and as normal subjects (10 subjects) if they denied such a history. Sample size calculation was based on a power of 80 % to find a difference of 20 %. Resting energy expenditure (REE) was assessed by indirect calorimetry and corrected for fat-free mass (FFM), which was assessed by bioelectric impedance analysis. RESULTS: REE was 1198 +/- 155 kilocalories (kcal) in vasospastics and 1169 +/- 122 in controls (Mann-Whitney U-test: p = 0.62). FFM was 39.6 +/- 3.3 kg in vasospastics and 41.1 +/- 2.3 kg in controls (Mann-Whitney U-test: p = 0.16). REE adjusted for FFM was 30.2 +/- 2.5 kcal/kg in vasospastics and 28.4 +/- 2.3 kcal/kg in controls (Mann-Whitney U-test: p = 0.08). CONCLUSIONS: Peripheral vasospastic syndrome seems not to be a secondary response to insufficient resting energy expenditure. The results of the present study rather indicate an opposite tendency which deserves further investigation.     

On the relevance of the long-time follow-up of the cyclocryotherapy

In spite of the availability of cyclocryodestructive laser therapy there still appears to be an indication for cyclocryotherapy in different kinds of glaucoma. PURPOSE: Cyclocryotherapy very often appears to be the operation of choice in cases of progressive functional visual loss if a patient is not sufficiently helped with the maximum tolerated medical therapy. We investigated long-term IOP effects and possible complications in our group of patients undergoing cyclocryotherapy. PATIENTS: Cyclocryotherapy was performed on 109 eyes of 97 patients from 1988 to 1994. Cyclocryotherapy was performed as follows: 67 of 109 eyes were controlled for IOP for an average of 10 months (3-41 months). We applied cryotherapy six times 3-4 mm behind the limbus for an average duration of 50 to 60 s over half of the circumference. RESULTS: We achieved satisfactory IOP control (IOP K 22 mm Hg) in 40 eyes, however, with 30 additional operations. One eye developed phthisis bulbi, and 3 other eyes became blind because of complications in neovascular glaucomas. Neovascular glaucoma cases responded the least. CONCLUSIONS: Cyclocryotherapy produced a statistically significant IOP reduction in eyes with primary open-angle glaucoma or secondary glaucoma. Close long-term follow-up appears advisable in order to check the eyes for possible increase in IOP or complications of surgery.     

On the relevance of the long-time follow-up of the cyclocryotherapy

In spite of the availability of cyclocryodestructive laser therapy there still appears to be an indication for cyclocryotherapy in different kinds of glaucoma.     

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

PURPOSE: A growing evidence in the scientific literature suggests that oxidative damage plays a pathogenic role in primary open-angle glaucoma. Therefore, it is of interest to test whether drugs effective against glaucoma display antioxidant activity. We test the hypothesis that the classic beta-blocker therapy for glaucoma with timolol involves the activation of antioxidant protective mechanisms towards endothelial cells.METHODS: Oxidative stress was induced in cultured human endothelial cells by iron/ascorbate with or without timolol pretreatment. Analysed parameters included cell viability (neutral red uptake and tetrazolium salt tests), lipid peroxidation (thiobarbituric reactive substances), and occurrence of molecular oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine).RESULTS: Oxidative stress decreased 1.8-fold cell viability, increased 3.0-fold lipid peroxidation and 64-fold oxidative damage to DNA. In the presence of timolol, oxidative stress did not modify cell viability, whereas lipid peroxidation was increased 1.3-fold, and DNA oxidative damage 3.6-fold only.CONCLUSIONS: The obtained results indicate that timolol exerts a direct antioxidant activity protecting human endothelial cells from oxidative stress. These cells employ mechanisms similar to those observed in the vascular endothelium. It is hypothesized that this antioxidant activity is involved in the therapeutic effect of this drug against glaucoma.     

Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma

PURPOSE: To assess the impact of vascular dysregulation on choroidal blood flow response to the hand-grip test and the relevance of this response to glaucoma. METHODS: Eighty healthy volunteers underwent a hand-grip test while choroidal blood flow was measured by means of laser Doppler flowmetry. Blood pressure, heart rate, and intraocular pressure (IOP) were monitored. Choroidal blood flow changes were compared between subjects with a positive history of cold hands and control subjects by means of analysis of variance. The relationship of the vascular response to the level of IOP at which progressive damage occurred was analyzed in 21 patients with primary open-angle glaucoma who had progressive damage despite normal or normalized IOP. RESULTS: Blood pressure and heart rate increased and IOP decreased in response to a hand-grip test. Healthy subjects with a positive history of cold hands (n = 36) demonstrated a decrease in choroidal blood flow during the hand-grip test (mean +/- SD: 13.5 +/- 5.8, 12.2 +/- 6.8, and 13.4 +/- 6.9 AU, at baseline, during the test, and 3 minutes after release, respectively), whereas control subjects (n = 44) demonstrated an inverse (12.5 +/- 8.3, 13.7 +/- 9.4, and 11.9 +/- 7.1 AU, respectively) response pattern (P = 0.039). Glaucoma patients with a decrease of at least 10% in choroidal blood flow during the hand-grip test had lower IOP (14.67 +/- 3.83 and 13.50 +/- 2.59 mm Hg in the right and the left eyes, respectively) compared (P = 0.032) with those without such a decrease (16.54 +/- 3.85 and 16.92 +/- 2.95 mm Hg in the right and the left eyes, respectively). CONCLUSIONS: A hand-grip test elicits a different blood flow response in subjects with vasospasm compared with control subjects. Damage by glaucoma in patients with a decrease in choroidal blood flow during a hand-grip test may progress at a relatively lower IOP.